Microscopy has provided valuable biological information by optically magnifying images of small structures in fixed cells and tissues. However, the resolution of such imaging techniques are restricted to approximately half the wavelength of the illuminating source. In the visible region of the spectrum this is on the order of a quarter to a third of a micron (250-330 nm). Unfortunately, there is a vast range of biological structures/systems where non-invasive observations below this length scale are inaccessible to conventional optical microscopy.
There has been considerable activity aimed at developing optical techniques that reveal structure on the 100 nm length scale and below. For example, the development of super-resolution microscopy allowed for the visualization of a sample with resolution better than 250 nanometers and down to 20 nm. However, these techniques require specialized and demanding imaging conditions, specially designed fluorescent proteins, or expensive new machines and additional technical training to use the machines, and has difficulty with thick structures such as tissue sections or tumors.
Thus, there is a need for higher resolution microscopy that can work with current diffraction limited microscopes and can optically magnify larger samples, such as tissue sections or tumors, with nanoscale precision.